Skip to main content

Main menu

  • Home
  • COVID-19
    • Articles & podcasts
    • Blog posts
    • Collection
    • News
  • Content
    • Current issue
    • Past issues
    • Early releases
    • Collections
    • Sections
    • Blog
    • Infographics & illustrations
    • Podcasts
    • Classified ads
  • Authors
    • Overview for authors
    • Submission guidelines
    • Submit a manuscript
    • Forms
    • Editorial process
    • Editorial policies
    • Peer review process
    • Publication fees
    • Reprint requests
  • CMA Members
    • Overview for members
    • Earn CPD Credits
    • Print copies of CMAJ
    • Career Ad Discount
  • Subscribers
    • General information
    • View prices
  • Alerts
    • Email alerts
    • RSS
  • JAMC
    • À propos
    • Numéro en cours
    • Archives
    • Sections
    • Abonnement
    • Alertes
  • CMAJ JOURNALS
    • CMAJ Open
    • CJS
    • JAMC
    • JPN

User menu

Search

  • Advanced search
CMAJ
  • CMAJ JOURNALS
    • CMAJ Open
    • CJS
    • JAMC
    • JPN
CMAJ

Advanced Search

  • Home
  • COVID-19
    • Articles & podcasts
    • Blog posts
    • Collection
    • News
  • Content
    • Current issue
    • Past issues
    • Early releases
    • Collections
    • Sections
    • Blog
    • Infographics & illustrations
    • Podcasts
    • Classified ads
  • Authors
    • Overview for authors
    • Submission guidelines
    • Submit a manuscript
    • Forms
    • Editorial process
    • Editorial policies
    • Peer review process
    • Publication fees
    • Reprint requests
  • CMA Members
    • Overview for members
    • Earn CPD Credits
    • Print copies of CMAJ
    • Career Ad Discount
  • Subscribers
    • General information
    • View prices
  • Alerts
    • Email alerts
    • RSS
  • JAMC
    • À propos
    • Numéro en cours
    • Archives
    • Sections
    • Abonnement
    • Alertes
  • Visit CMAJ on Facebook
  • Follow CMAJ on Twitter
  • Follow CMAJ on Pinterest
  • Follow CMAJ on Youtube
  • Follow CMAJ on Instagram
Commentary

Combination measles–mumps–rubella–varicella vaccination and the risk of febrile seizure

Karina A. Top and Noni E. MacDonald
CMAJ August 05, 2014 186 (11) 812-813; DOI: https://doi.org/10.1503/cmaj.140778
Karina A. Top
Department of Pediatrics (Top, MacDonald) and Department of Community Health & Epidemiology (Top), Dalhousie University, Halifax, NS
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: karina.top@dal.ca
Noni E. MacDonald
Department of Pediatrics (Top, MacDonald) and Department of Community Health & Epidemiology (Top), Dalhousie University, Halifax, NS
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Tables
  • Related Content
  • Responses
  • Metrics
  • PDF
Loading

See related research article on page 824 and at www.cmaj.ca/lookup/doi/10.1503/cmaj.140078

Vaccination programs are a highly effective public health intervention, having led to dramatic reductions in childhood morbidity and mortality. However, as the recent measles outbreaks in Canada have illustrated,1 control of vaccine-preventable diseases can be maintained only through continued high public acceptance of — and confidence in — vaccination programs. Postlicensure surveillance and evaluation of vaccine safety are two key components for maintaining public confidence in vaccines and ensuring that vaccination programs continue to provide the maximal benefit to society at minimal risk.

In a related article in CMAJ, MacDonald and colleagues2 report the findings of their population-based cohort study involving nearly 280 000 children in Alberta in which they compared the risk of seizures in children 12–23 months of age who received the combination measles–mumps–rubella–varicella (MMRV) vaccine (Priorix-Tetra, GlaxoSmith-Kline) with the risk in those who received separate MMR and varicella (MMR+V) vaccines at the same visit. The study period from 2006 to 2012 spans the switch from separate MMR+V vaccines to the combination MMRV vaccine in 2010. The MMR vaccine is known to be associated with the phenomenon of febrile seizures, which are brief (≤15 min), generalized convulsions that occur in association with fever in children six months to five years of age.3,4 Although febrile seizures are generally benign and are not associated with long-term neurologic sequelae or developmental delay, they often frighten parents and prompt visits to the emergency department.3 The peak risk of fever after MMR coincides with the peak in viral replication on days 7–10 after vaccination; fever occurs in about 10% of children receiving the vaccine, of whom 0.3%–0.4% will have a febrile seizure.4,5 Fever and febrile seizure occur more commonly following the first dose than the second.5

MacDonald and colleagues2 compared the risk of ambulatory and inpatient visits for seizure 7–10 days after vaccination with the risk in the 42 days before vaccination. The authors determined that the relative risk of seizure was increased on days 7–10 in both the MMRV and MMR+V groups, as would be expected. However, the risk was twice as high after MMRV than after MMR+V (relative risk 1.99, 95% confidence interval [CI] 1.30–3.05, adjusted for age and calendar year). This translates to one additional febrile seizure for every 2841 MMRV doses administered. Of note, in children with a history of seizure or a seizure disorder, there was no difference in risk between the MMRV and MMR+V vaccines (relative risk 1.30, 95% CI 0.60–2.79).2

These findings are similar to those of population-based cohort studies conducted in the United States with a different MMRV formulation, Pro-Quad (Merck), which showed an excess risk of one febrile seizure per about 2300–2600 doses of MMRV, compared with separate MMR+V vaccines.4,6 MacDonald and colleagues’2 study is the first in Canada, and the largest study to date to assess this risk with the Priorix-Tetra formulation of MMRV. As the authors discuss, a recent matched-cohort study from Germany reported a 3.5-fold increase in febrile seizure on days 5–12 after vaccination with Priorix-Tetra (MMRV) versus MMR+V (odds ratio 3.5, 95% CI 0.7–19.0).7 The lack of a significant difference may be due to the inclusion of only patients admitted to hospital and of only children over four years of age, in whom the risk of febrile seizure after MMRV is not increased.8

In discussions of the risks of febrile seizure associated with MMR and MMRV, it is important to note that these risks are far lower than the risk of complications from measles, which occur in about 10% of cases.5 However, febrile seizures, although benign, are concerning to many parents. Some may perceive the risks of the vaccine as higher than the risks of disease. The health care costs associated with febrile seizures must also be considered when deciding which vaccine to use in children 12–23 months of age. As MacDonald and colleagues point out, the small increase in the risk of febrile seizures with MMRV must be balanced against the benefits of a single, combined vaccination that reduces the number of injections young children will require, the latter a concern for many parents. Canadian data are lacking regarding parental attitudes and perceptions of the risks and benefits of MMRV versus MMR+V. This is therefore an important research priority to ensure policies are based on the best evidence.

In countries currently vaccinating children against varicella, further research is needed to determine the optimal schedule for MMR+V vaccination. Canada is uniquely positioned to evaluate the safety and effectiveness of different MMR, varicella and MMRV schedules because of the 13 different vaccination schedules used across the country, one for each province and territory (Appendix 1, available at www.cmaj.ca/lookup/suppl/doi:10.1503/cmaj.140778/-/DC1).9 Seven provinces currently administer MMRV at 12 months of age, and four administer MMRV as the second dose at 18 months of age. Data are lacking on the safety and acceptability of several of these schedules.

A hybrid program of separate MMR+V vaccines for the first doses, followed by MMRV for the second dose may end up achieving the optimal balance of risks and benefits. This approach may be more costly to the public health system because of the need to purchase MMR, varicella and MMRV vaccines, but the costs may be offset by decreased emergency visits for febrile seizure and improved confidence in vaccination. Decision-making regarding MMR+V vaccination will thus benefit from further research in three key areas: evaluation of vaccine safety, public acceptability of the risks and benefits of the different schedules, and cost-effectiveness of the different schedules.

KEY POINTS
  • A population-based cohort study from Alberta involving children 12–23 months of age reported an excess risk of febrile seizure after measles–mumps–rubella–varicella (MMRV) vaccination of 1 per 2841 doses, compared with separate MMR and varicella (MMR+V) vaccinations.

  • These findings support those from other countries using different formulations of MMRV.

  • More research is needed to determine the optimal schedule for MMR and varicella vaccination that balances risks, benefits, costs, parental attitudes and public acceptability, and Canada is in a unique position to address these issues.

Footnotes

  • Competing interests: None declared.

  • This article was solicited and has not been peer reviewed.

  • Contributors: Karina Top drafted the article, which both authors revised and approved for publication.

References

  1. ↵
    1. Deehan H,
    2. Shane A
    . Measles activity in Canada: January - June 2014. Can Commun Dis Rep 2014;40-12:233–5.
    OpenUrl
  2. ↵
    1. MacDonald SE,
    2. Dover DC,
    3. Simmonds KA,
    4. et al
    . Risk of febrile seizures after first dose of measles–mumps–rubella–varicella vaccine: a population-based cohort study. CMAJ 2014 June 9 [Epub ahead of print].
  3. ↵
    1. Friedman MJ,
    2. Sharieff GQ
    . Seizures in children. Pediatr Clin North Am 2006;53:257–77.
    OpenUrlCrossRefPubMed
  4. ↵
    1. Klein NP,
    2. Fireman B,
    3. Yih WK,
    4. et al
    . Measles-mumps-rubella-varicella combination vaccine and the risk of febrile seizures. Pediatrics 2010;126:e1–8.
    OpenUrlAbstract/FREE Full Text
  5. ↵
    1. Strebel PM,
    2. Papania MJ,
    3. Parker Fiebelkorn A,
    4. et al
    . Measles vaccine. In: Plotkin SA, Orenstein WA, Offit PA, editors. Vaccines. 6th ed. Philadelphia (PA): Saunders Elsevier; 2013.
  6. ↵
    1. Jacobsen SJ,
    2. Ackerson BK,
    3. Sy LS,
    4. et al
    . Observational safety study of febrile convulsion following first dose MMRV vaccination in a managed care setting. Vaccine 2009;27:4656–61.
    OpenUrlCrossRefPubMed
  7. ↵
    1. Schink T,
    2. Holstiege J,
    3. Kowalzik F,
    4. et al
    . Risk of febrile convulsions after MMRV vaccination in comparison to MMR or MMR+V vaccination. Vaccine 2014;32:645–50.
    OpenUrlCrossRefPubMed
  8. ↵
    1. Klein NP,
    2. Lewis E,
    3. Baxter R,
    4. et al
    . Measles-containing vaccines and febrile seizures in children age 4 to 6 years. Pediatrics 2012;129:809–14.
    OpenUrlAbstract/FREE Full Text
  9. ↵
    Publicly funded immunization programs in Canada - routine schedule for infants and children including special programs and catch-up programs (as of March 2014). Ottawa: Public Health Agency of Canada; 2014. Available: www.phac-aspc.gc.ca/im/ptimprog-progimpt/table-1-eng.php (updated 2014 Mar. 17; accessed 2014 June 12).
PreviousNext
Back to top

In this issue

Canadian Medical Association Journal: 186 (11)
CMAJ
Vol. 186, Issue 11
5 Aug 2014
  • Table of Contents
  • Index by author

Article tools

Respond to this article
Print
Download PDF
Article Alerts
To sign up for email alerts or to access your current email alerts, enter your email address below:
Email Article

Thank you for your interest in spreading the word on CMAJ.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Combination measles–mumps–rubella–varicella vaccination and the risk of febrile seizure
(Your Name) has sent you a message from CMAJ
(Your Name) thought you would like to see the CMAJ web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Combination measles–mumps–rubella–varicella vaccination and the risk of febrile seizure
Karina A. Top, Noni E. MacDonald
CMAJ Aug 2014, 186 (11) 812-813; DOI: 10.1503/cmaj.140778

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
‍ Request Permissions
Share
Combination measles–mumps–rubella–varicella vaccination and the risk of febrile seizure
Karina A. Top, Noni E. MacDonald
CMAJ Aug 2014, 186 (11) 812-813; DOI: 10.1503/cmaj.140778
Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Footnotes
    • References
  • Figures & Tables
  • Related Content
  • Responses
  • Metrics
  • PDF

Related Articles

  • Risk of febrile seizures after first dose of measles–mumps–rubella–varicella vaccine: a population-based cohort study
  • PubMed
  • Google Scholar

Cited By...

  • No citing articles found.
  • Google Scholar

More in this TOC Section

  • Transforming race-based health research in Canada
  • Not neutral: reimagining antiracism as a professional competence
  • Time to dismantle systemic anti-Black racism in medicine in Canada
Show more Commentary

Similar Articles

Collections

  • Topics
    • Vaccination
    • Pediatrics
    • Neurology

Content

  • Current issue
  • Past issues
  • Collections
  • Sections
  • Blog
  • Podcasts
  • Alerts
  • RSS
  • Early releases

Information for

  • Advertisers
  • Authors
  • Reviewers
  • CMA Members
  • Media
  • Reprint requests
  • Subscribers

About

  • General Information
  • Journal staff
  • Editorial Board
  • Governance Council
  • Journal Oversight
  • Careers
  • Contact
  • Copyright and Permissions

Copyright 2021, Joule Inc. or its licensors. All rights reserved. ISSN 1488-2329 (e) 0820-3946 (p)

All editorial matter in CMAJ represents the opinions of the authors and not necessarily those of the Canadian Medical Association or its subsidiaries.

Powered by HighWire